Age-related Macular Degeneration (AMD) is widely acknowledged as a principal cause of vision loss in the elderly. Currently, the therapeutic interventions available in clinical practice fail to achiev Show more
Age-related Macular Degeneration (AMD) is widely acknowledged as a principal cause of vision loss in the elderly. Currently, the therapeutic interventions available in clinical practice fail to achieve satisfactory outcomes. Therefore, it is imperative that we approach the progress of AMD from novel perspectives in order to explore new therapeutic strategies. We obtained transcriptomic data from the macular and the peripheral retina from patients with AMD and a control group from the Gene Expression Omnibus (GEO) database. Through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we identified differentially expressed genes (DEGs) that were significantly enriched in functions associated with ferroptosis. Subsequent application of machine learning techniques enabled the identification of key hub genes, whose diagnostic potential was further validated. Additionally, the expression of these hub genes was corroborated in both animal and cellular models. Finally, we performed a functional enrichment analysis of these hub genes. In the macula of patients with AMD, 452 DEGs were identified, while in the peripheral retina, 222 DEGs were discovered. Within the macula, 19 genes were associated with ferroptosis, compared to 3 in the peripheral retina. Consequently, the macular was selected as the primary focus of the study. Subsequent screening of these 19 genes using LASSO regression, Support Vector Machine (SVM), and Random Forest algorithms identified four hub genes: FADS1, TFAP2A, AKR1C3, and TTPA. Consequently, we utilized cigarette smoke extract (CSE) to either stimulate retinal pigment epithelial (RPE) cells in vitro or administer it via intravitreal injection, thereby establishing in vitro and in vivo models of AMD. Results from RT-PCR and Western blot analyses revealed an upregulation of FADS1, AKR1C3, and TTPA, while TFAP2A exhibited decreased expression. Finally, we investigated the infiltration of immune cells within the macular and performed a functional enrichment analysis of the hub genes. We identified four key ferroptosis-related genes (FRGs)-FADS1, AKR1C3, TFAP2A, and TTPA-that possess diagnostic relevance for AMD and correlate with immune cell infiltration. Moreover, significant changes in both mRNA and protein expression levels of these genes have been observed in in vitro experiments and mice models. Show less
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregn Show more
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregnancy women and 317 healthy non-pregnant women. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and hypersensitive C-reactive protein (hs-CRP) were measured in both groups. The mean and standard deviation of each index were calculated to establish the reference range of normal serum lipid levels in pregnant women in mid-to-late pregnancy. The associations between serum lipid levels and perinatal outcomes were assessed statistically. There were no significant differences in age, pregnancy, or parity between the adverse outcome and normal delivery groups, but the caesarean section rate was significantly higher in the adverse outcome group. The levels of hs-CRP, TG, TC, HDL-C, LDL-C, and ApoA1 were significantly higher in the adverse outcome group. Elevated hs-CRP, TG, and HDL-C levels were risk factors for adverse pregnancy outcomes. According to the receiver operating characteristic curve, the optimal threshold of the combined diagnosis of these three indicators to predict adverse pregnancy outcomes was 0.534, and the area under the curve was 0.822. The establishment of lipid reference intervals in the second and third trimesters of pregnancy can effectively evaluate lipid metabolism in pregnant women, and the measurement of lipid metabolism in pregnant women is helpful in predicting adverse pregnancy outcomes. Show less
Mei-Jun Lyu, Dong-Yu Min, Lian-Qun Jia+2 more · 2025 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
To explore the mechanism of astragaloside Ⅳ in regulating energy metabolic reprogramming, alleviating endothelial-to-mesenchymal transition(EndMT), and preventing atherosclerosis(AS) in ApoE~(-/-) AS Show more
To explore the mechanism of astragaloside Ⅳ in regulating energy metabolic reprogramming, alleviating endothelial-to-mesenchymal transition(EndMT), and preventing atherosclerosis(AS) in ApoE~(-/-) AS mice, ApoE~(-/-) AS mouse models were established by high-fat feeding and randomly divided into three groups: model group, astragaloside Ⅳ group, and blank control group. The mice in the astragaloside Ⅳ group were administered astragaloside Ⅳ via gavage at a dose of 40 mg·kg~(-1)·d~(-1), while mice in the blank control group and model group received an equal volume of normal saline via gavage for four consecutive weeks. The blood lipid levels of mice in each group were measured using an automatic biochemical analyzer. Hematoxylin-eosin(HE) staining was used to observe the pathomorphological changes in the mouse aorta. The degree of EndMT was detected by immunofluorescence, and the protein expression levels of α-smooth muscle actin(α-SMA) and vascular endothelial cadherin(VE-cadherin) in the aorta were detected by Western blot. Targeted energy metabolomics technology was used to qualitatively and quantitatively analyze the spectrum of serum energy metabolites in mice, followed by KEGG pathway enrichment analysis of differential metabolites. The expression of glycolysis-related genes was detected using RT-PCR. The results showed that astragaloside Ⅳ significantly reduced the levels of serum total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-C) while increasing high-density lipoprotein cholesterol(HDL-C) levels. It reduced atherosclerotic plaque formation, decreased the number of α-SMA and VE-cadherin double staining positive cells, downregulated the protein expression of mesenchymal cell surface antigen α-SMA, and upregulated the protein expression of endothelial cell surface antigen VE-cadherin. Targeted energy metabolomics analysis shows that astragaloside Ⅳ restored nine altered energy metabolites in the serum. The pathway enrichment analysis indicated that serum differential metabolites were mainly enriched in glycolytic pathways. RT-PCR detection revealed that astragaloside Ⅳ significantly downregulated the mRNA expression of key glycolytic enzymes, including hexokinase-Ⅱ(HK-Ⅱ), phosphofructokinase(PFKM), and pyruvate kinase M2(PKM2). These results suggest that astragaloside Ⅳ may ameliorate AS by inhibiting the excessive activation of glycolysis, modulating energy metabolic reprogramming, and alleviating EndMT. Show less
Excessive hepatic lipid accumulation is the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), yet its underlying mechanisms still not fully understood. In this study, we id Show more
Excessive hepatic lipid accumulation is the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), yet its underlying mechanisms still not fully understood. In this study, we identified RNA binding motif protein 39 (Rbm39) as a key modulator of hepatic lipid homeostasis during MASLD progression. To establish in vivo MASLD model, mice were fed either a high-fat diet (HFD) or a Gubra-Amylin NASH (GAN) diet. We employed adeno-associated virus to manipulate Rbm39 expression levels to assess its role in MASLD. Transcriptome analysis was conducted to pinpoint the genes targeted by Rbm39. Western blot, RT-PCR, dual-luciferase reporter gene assays, and alternative splicing analysis were utilized to delve into the molecular mechanisms. Our results showed that Rbm39 expression was notably decreased in the livers of MASLD mice. Knockdown of hepatic Rbm39 aggravated HFD-induced hepatic steatosis and GAN diet-induced MASH, along with a notable decrease in serum lipid levels. Conversely, overexpression of Rbm39 attenuated MASLD development and progression. RNA sequencing data analysis indicated that Rbm39 regulated the expression of apolipoprotein B (Apob) and fatty acid-binding protein 4 (Fabp4), both of which are crucial for lipid transport. Mechanistically, Rbm39 enhanced the transcription of Apob by upregulating hepatocyte nuclear factor 4α (Hnf4α), while it suppressed Fabp4 transcription by regulating alternative splicing of hypoxia inducible factor-1α (Hif-1α). These findings highlight the pivotal role of Rbm39 in maintaining hepatic lipid homeostasis and suggest its potential as a therapeutic target for MASLD. Show less
2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is a common environmental contaminant and widely detected in aquatic surroundings, while only a few reports exist on the hazard mechanism in economic aquati Show more
2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is a common environmental contaminant and widely detected in aquatic surroundings, while only a few reports exist on the hazard mechanism in economic aquatic animals. It has been shown that 40 and 4000 ng/g of BDE-47 dietary exposure over 42 days significantly increased the levels of blood triglycerides, glucose, and liver glycogen in carp ( Show less
We report a diagnostically challenging case of acute myeloid leukemia (AML) in a 2-year-9-month-old boy, presenting with diarrhea and pancytopenia. Bone marrow aspiration revealed 90% blasts exhibitin Show more
We report a diagnostically challenging case of acute myeloid leukemia (AML) in a 2-year-9-month-old boy, presenting with diarrhea and pancytopenia. Bone marrow aspiration revealed 90% blasts exhibiting cup-like nuclei and azurophilic granules, morphologically mimicking acute promyelocytic leukemia (APL).However, immunophenotyping was inconsistent with classic APL, showing positivity for CD33 and cytoplasmic myeloperoxidase (cMPO) but negativity for CD34 and HLA-DR. Molecular analysis was negative for the canonical PML::RARA fusion but identified a rare Show less
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from Show more
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from colorectal cancer (CRLM) remain poorly understood. Here we show that patients with CRLM whose liver metastases (LM) exhibited tumor fibrosis (Fibrosis+ LM) had significantly worse progression-free survival (P = 0.025) and overall survival (P = 0.008). Single-cell RNA sequencing revealed that the tumor microenvironment of the Fibrosis+ LM was characterized by T cells with an exhausted phenotype, macrophages displaying a profibrotic and suppressive phenotype and fibrosis-promoting fibroblasts. Further investigation highlighted the pivotal role of VCAN_eCAF in remodeling the tumor fibrosis in the tumor microenvironment of Fibrosis+ LM, emphasizing potential targetable interactions such as FGF23 or FGF3-FGFR1. Validation through multiplex immunohistochemistry/immunofluorescence and spatial transcriptomics supported these findings. Here we present a comprehensive single-cell atlas of tumor fibrosis in LM, revealing the intricate multicellular environment and molecular features associated with it. These insights deepen our understanding of tumor fibrosis mechanisms and inform improved clinical diagnosis and treatment strategies. Show less
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein in Show more
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein interactions. In this study, we investigate the role of the PALS1-associated tight junction protein (PATJ), which contains 10 PDZ domains, in the formation of IS and its subsequent impact on T cell activation. To elucidate the function of PATJ, we generated murine models with conditional T cell-specific knockout of We observed a rapid increase in PATJ expression during T cell activation. Conditional knockout of Our study reveals an important role of PATJ in the formation of IS and provides an approach to improve the efficacy of CAR-T therapy. Show less
Atherosclerosis (AS) is a chronic inflammatory disorder driven by dysregulated lipid metabolism and remains a leading cause of cardiovascular morbidity. The Shen-Hong-Tong-Luo (SHTL) preparation has d Show more
Atherosclerosis (AS) is a chronic inflammatory disorder driven by dysregulated lipid metabolism and remains a leading cause of cardiovascular morbidity. The Shen-Hong-Tong-Luo (SHTL) preparation has demonstrated clinical benefit in stabilizing atherosclerotic plaques, yet its molecular mechanisms are not fully defined. This research sought to elucidate the protective effects exerted by SHTL on AS progression. To investigate the impact of SHTL on macrophage function and plaque stability, we utilized ApoE SHTL markedly attenuated the progression of AS, demonstrated by reduced plaque formation within both the aortic root and aorta, diminished plasma lipid concentrations, and suppressed inflammatory responses. SHTL demonstrates significant anti-inflammatory and lipid-regulatory effects, attenuating AS progression through the PPARγ/Mfge8 pathway, thereby enhancing macrophage efferocytosis. These findings highlight a novel mechanism by which SHTL may contribute to preventing and treating atherosclerotic diseases. Show less
Scatophagus argus is a highly valuable aquaculture fish. Its artificial breeding faces problems in the induction of high quality eggs, thus necessitating studies on the regulation of ovarian developme Show more
Scatophagus argus is a highly valuable aquaculture fish. Its artificial breeding faces problems in the induction of high quality eggs, thus necessitating studies on the regulation of ovarian development. As the centre of nutrient metabolism in fish, the liver provides the material basis for ovarian development. However, the molecular mechanism of the liver in ovarian development in S. argus is still unclear. In this study, a transcriptome analysis of adult S. argus livers at different stages of ovarian development (stages II, III and IV) was performed. 410, 1025 and 1867 differentially expressed genes (DEGs) were obtained between stages II and III, stages II and IV and stages III and IV, respectively. In GO and KEGG analyses, DEGs were mostly involved in vitellogenesis and egg envelope formation (e.g., erα, erβ1, vtga, vtgb, vtgc, zp3, zp4a and zp4b), lipid metabolism and energy metabolism (e.g., dagt1, dagt2, lpl, apob, hk1, acly, ogdh, pc, and fbp1), and hormone signaling (e.g., lepa and igfbp1). Additionally, genes that were significantly upregulated in the liver at stage IV of ovarian development, compared to stages II and III, were markedly enriched in steroid biosynthesis and metabolism pathways. These findings provide clues to understanding the mechanisms of liver action in teleost ovarian development. Show less
Ttraumatic brain injury (TBI) induces oxidative stress, which contributes to neuronal damage and cognitive impairment. Apolipoprotein E (ApoE) plays a key role in neural repair and may modulate oxidat Show more
Ttraumatic brain injury (TBI) induces oxidative stress, which contributes to neuronal damage and cognitive impairment. Apolipoprotein E (ApoE) plays a key role in neural repair and may modulate oxidative stress responses. However, the relationship between ApoE expression at different stages after TBI and oxidative stress markers, as well as its association with cognitive outcomes, remains unclear. A total of 126 patients with TBI were prospectively enrolled and stratified according to the Glasgow Coma Scale (GCS) score on admission into mild ( Serum ApoE levels peaked at 24 h and slightly decreased thereafter, with overall levels increasing in proportion to TBI severity ( ApoE exhibits an injury-severity-dependent increase during the early stage of TBI, and its levels are closely associated with oxidative stress imbalance and cognitive impairment. These findings suggest that ApoE may play a critical role in both the pathological progression and neural repair following TBI. Show less
This study aims to establish a hypoxia-immune-related gene signature within the tumor microenvironment (TME) to reliably predict prognosis in non-small cell lung cancer (NSCLC). Transcriptomic profile Show more
This study aims to establish a hypoxia-immune-related gene signature within the tumor microenvironment (TME) to reliably predict prognosis in non-small cell lung cancer (NSCLC). Transcriptomic profiles and clinical data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (GSE74777, GSE68465). Hypoxia- and immune-related genes were curated from MSigDB, ImmPort, and INATDB. Prognostic genes were identified via Cox and LASSO regression analyses, and a risk model was constructed. Model validity was assessed through Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, and external validation. An eight-gene prognostic signature (AKAP12, MT2A, SERPINE1, CD1E, CD79A, CXCL13, XCL2, ANGPTL4) was established. The model demonstrated significant predictive accuracy for NSCLC survival (AUC: 0.643/0.649/0.620 at 1/3/5 years in TCGA cohort). Patients with high immune activity exhibited superior survival outcomes compared to those with low-immune counterparts (log-rank P < 0.001). Multivariate Cox regression confirmed the risk score as an independent prognostic factor (HR = 1.82, 95% CI: 1.44-2.30, P < 0.001). The hypoxia-immune microenvironment signature serves as a robust prognostic classifier for NSCLC, providing a quantitative framework for personalized risk stratification and clinical decision support. Show less
This study aims to elucidate the effects of arecaidine on oral mucosa through RNA sequencing (RNA-Seq) combined with in vivo and in vitro experimental validation. Based on transcriptomic analysis, we Show more
This study aims to elucidate the effects of arecaidine on oral mucosa through RNA sequencing (RNA-Seq) combined with in vivo and in vitro experimental validation. Based on transcriptomic analysis, we preliminarily explored the molecular targets and mechanisms by which arecaidine influences oral mucosa. Subsequent validation was performed using arecaidine-treated human primary oral mucosal fibroblasts. In vivo experiments revealed that the arecaidine-treated group exhibited significantly restricted oral cavity opening compared to the control group, with markedly reduced mouth-opening values. Histopathological analysis via HE staining and Masson staining demonstrated fibrotic lesions in the arecaidine-treated group. RNA-Seq libraries constructed from oral mucosal tissues identified 100 significantly differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that arecaidine influenced multiple pathways, including autoimmune thyroid disease, allograft rejection, type I diabetes, graft-versus-host disease, and the PPAR-γ signaling pathway. Notably, arecaidine significantly downregulated PPAR-γ, PCK1, pdk4, plin5, Hmgcs2, UCP3, and Angptl4, while upregulating TGF-β1, FOS, and other genes associated with the PPAR pathway. In vitro experiments confirmed that arecaidine induced substantial damage to fibroblasts, suppressing proliferation and promoting the secretion of inflammatory cytokines (e.g., IL-6, TGF-β, TNF-α) after 48 h exposure to high concentrations. Furthermore, arecaidine significantly altered the expression of molecules linked to the PPAR-γ signaling pathway. This study delineates the transcriptomic response of oral mucosa to arecaidine through integrated in vivo and in vitro experiments, confirming its role in inducing submucosal fibrosis. The underlying mechanism is associated with dysregulation of the PPAR-γ signaling pathway. Show less
Given the lack of evidence, we cannot definitively determine the relationship between attachment networks and problematic mobile phone use, hindering effective intervention strategies. Therefore, a th Show more
Given the lack of evidence, we cannot definitively determine the relationship between attachment networks and problematic mobile phone use, hindering effective intervention strategies. Therefore, a three-wave longitudinal study was designed to explore the heterogeneity of parent-child attachment networks using latent profile analysis (LPA) and random intercept latent transition analysis (RI-LTA). Participants included 2116 adolescents (ages 14-21; 53.8% girls). Results identified five stable parent-child attachment network profiles, each showing moderate but decreasing stability. Notably, adolescents who were grouped into an attachment network characterized by secure maternal attachment but insecure paternal attachment, similar to those in attachment networks with both insecure maternal and paternal attachment, scored higher levels of problematic mobile phone use than those who were grouped into attachment networks with both secure maternal and paternal attachment. Our findings fill empirical gaps and provide strong evidence supporting attachment-based interventions to reduce problematic mobile phone use. Show less
Stroke, including cerebral ischemia and cerebral hemorrhage, is one of the leading causes of mortality worldwide. The narrow therapeutic window limits the efficacy and applicability of current treatme Show more
Stroke, including cerebral ischemia and cerebral hemorrhage, is one of the leading causes of mortality worldwide. The narrow therapeutic window limits the efficacy and applicability of current treatments such as thrombolysis and endovascular thrombectomy. This urgent need for effective therapies has shifted the focus towards mitigating the secondary inflammation and tissue damage that follow intracerebral hemorrhage. Spatial transcriptomic analysis of mouse brains post-ischemia has revealed that the ApoE-TREM2 signaling pathway is central to the complex interactions between microglia and various surrounding cells, coordinating the formation of neuroglial scars, suggesting that TREM2 is a key participant in post-stroke pathology and a potential therapeutic target. This review aims to provide an insightful synthesis of TREM2, including its structure, signaling pathways, and the role of its soluble form, sTREM2, in the nervous system. We systematically summarize the signaling pathways and mechanisms by which TREM2 modulates microglial function, including promoting phagocytosis, exerting anti-inflammatory properties, modulating lipid metabolism, and enhancing cell survival. We also highlight the TREM2's interactions with other cell types post-stroke, such as macrophages and B cells. Furthermore, we discuss advancements in TREM2-targeted drug development, emphasizing the potential of TREM2 agonists and antibodies to modulate microglial function and inflammation, which sets the stage for future research and drug development. Show less
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathologic Show more
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits. Show less
Acute respiratory distress syndrome (ARDS) is a lung inflammatory condition associated with the accumulation of fluid edema and cell infiltrates into the alveolar space along with dysregulation of the Show more
Acute respiratory distress syndrome (ARDS) is a lung inflammatory condition associated with the accumulation of fluid edema and cell infiltrates into the alveolar space along with dysregulation of the immune response. Current therapeutics are limited to palliative care, i.e., mechanical ventilators, thus highlighting the need to develop targeted therapeutic for ARDS. Interleukin-27 (IL-27) is a multifunctional cytokine with the capability for immune modulation. Our interest lies in exploring the properties of IL-27, particularly as an anti-inflammatory cytokine that functions as an antagonist of IL-6 signaling, as an inducer of anti-viral genes, as a promoter of tissue repair, and as a regulator of both the innate and adaptive immune responses, possessing promising potential as a therapeutic for ARDS. To overcome the challenge of repeated administration due to the short half-life of cytokines, we utilized a cell-based gene therapy approach. An IL-27-expressing plasmid was transfected into adipose mesenchymal stromal cells (ASC) that serve as the gene therapy carriers. For in vitro studies, we treated mono- and co-culture lung lipopolysaccharide (LPS)-induced lung epithelial and monocytes/macrophages cell line with IL-27-expressing ASC (IL-27 ASC) conditioned media (CM) to determine the effects on pro-inflammatory gene expression. For in vivo studies, male C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) and treated either PBS, ASC, or IL-27 ASC (5 × 10 IL-27 ASC CM reduced pro-inflammatory gene expression of lung epithelial and macrophages cultured in both mono- and co-culture systems. Additionally, IL-27 ASC were able to reduce pro-inflammatory markers, decrease cell infiltration into the lungs, promote genes and immune cells involved in tissue repair, and rebalance innate and adaptive immunity in an LPS-induced in vivo model. Collectively, our in vitro and in vivo results show promising potential for IL-27 cell-based gene therapy as a treatment for ARDS. Show less
Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac h Show more
Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac hypertrophy. SMURF2 (SMAD-specific E3 ubiquitin ligase 2) is an important member of NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) family of HECT E3 ubiquitin ligases. In this study we investigated the regulatory role of SMURF2 in cardiac hypertrophy. Experiment models were established in mice by transverse aortic constriction (TAC) in vivo, as well as in neonatal rat cardiomyocytes (NRCMs) by treatment with angiotensin II (Ang II, 1 μM) in vitro. We showed that the expression levels of SMURF2 were significantly elevated in cardiac tissues from patients with cardiac hypertrophy and the two experiment models. In NRCMs, SMURF2 knockdown or treatment with a specific SMURF2 inhibitor heclin (8 μM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, evidenced by reduced mRNA levels of Anp, Bnp and β-Mhc as well as cell surface. Prophylactic or therapeutic administration of heclin (10 mg·kg Show less
Xueli Chen, Li Dai · 2025 · Biochemical genetics · Springer · added 2026-04-24
Asthma is a common chronic respiratory disease in children, the incidence rate of which has increased in recent years. Wilms tumour 1-associated protein (WTAP) is an N6-methyladenosine (m6A) methyltra Show more
Asthma is a common chronic respiratory disease in children, the incidence rate of which has increased in recent years. Wilms tumour 1-associated protein (WTAP) is an N6-methyladenosine (m6A) methyltransferase. The purpose of this study was to explore the specific mechanism of WTAP in asthma progression, and clarify the intricate interplay between m6A modifications, WTAP, AXIN1, and their collective impact on airway smooth muscle cells (ASMCs) proliferation in asthma. Platelet-derived growth factor-BB (PDGF-BB)-treated ASMCs were used to establish an asthma model in vitro. The cell phenotype was tested using CCK-8, transwell, and wound healing assays. The expression of the Wnt signalling pathway was detected by western blotting. In addition, the relationship between WTAP/YTDHF2 and AXIN1 was assessed by a double luciferase reporter assay. Actinomycin D treatment and RT‒qPCR assays were performed to determine the mRNA stability of AXIN1. We found that WTAP was significantly increased in PDGF-BB-treated ASMCs. Knockdown of WTAP inhibited the excessive cell viability and migration of ASMCs induced by PDGF-BB. Furthermore, WTAP knockdown increased AXIN1 levels and inhibited the Wnt signalling pathway. Furthermore, WTAP knockdown decreased the m6A levels and enhanced the mRNA stability of AXIN1. WTAP overexpression showed the opposite effect. In addition, YTHDF2 was demonstrated to be the reader that recognizes the WTAP-mediated m6A modification of AXIN1. YTHDF2 knockdown enhanced the mRNA stability of AXIN1 and reversed the effect of WTAP overexpression on PDGF-BB-treated ASMCs. WTAP knockdown inhibited the excessive cell viability and migration of ASMCs by enhancing the m6A levels of AXIN1, which was further recognized by YTHDF2. The upregulation of AXIN1 mediated by the WTAP/YTHDF2 axis further inhibited the Wnt signalling pathway. Our study provides a new method for the treatment of asthma. This work not only deepens our understanding of the molecular underpinnings of asthma but also identifies potential therapeutic targets for the development of novel treatments aimed at inhibiting ASMC proliferation and alleviating asthma symptoms. Show less
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompl Show more
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompletely defined. Here, we found that BAF60a functions as a chromatin regulator that sustains biphasic GSIS and preserves β cell function under metabolic stress conditions. BAF60a was downregulated in β cells from obese and diabetic mice, monkeys, and humans. β cell-specific inactivation of BAF60a in adult mice impaired GSIS, leading to hyperglycemia and glucose intolerance. Conversely, restoring BAF60a expression improved β cell function and systemic glucose homeostasis. Mechanistically, BAF60a physically interacted with Nkx6.1 to selectively modulate chromatin accessibility and transcriptional activity of target genes critical for GSIS coupling in islet β cells. A BAF60a V278M mutation associated with decreased β cell GSIS function was identified in human donors. Mice carrying this mutation, which disrupted the interaction between BAF60a and Nkx6.1, displayed β cell dysfunction and impaired glucose homeostasis. In addition, GLP-1R and GIPR expression was significantly reduced in BAF60a-deficient islets, attenuating the insulinotropic effect of GLP-1R agonists. Together, these findings support a role for BAF60a as a component of the epigenetic machinery that shapes the chromatin landscape in β cells critical for glucose sensing and insulin secretion. Show less
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of Show more
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of chlorogenic acid (CHA), a multifunctional natural active compound, in AD therapy by developing a trifunctional nanocarrier (MC-H/R/si). CHA was effectively conjugated with iron-based metal-organic frameworks (MIL/Fe-100) through chelation interaction. The resulting nanocomplex (MC) not only enhances the bioavailability of CHA but also facilitates a synergistic antioxidant effect between CHA and MIL/Fe-100. Importantly, CHA can chelate Zn Show less
Epidemiology has shown a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. However, it remains unknown whether PM aggravates myocardial ischemia-reperfusion Show more
Epidemiology has shown a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. However, it remains unknown whether PM aggravates myocardial ischemia-reperfusion (I/R) injury, and the related mechanisms are unclear. Our previous study has shown that adipose stem cell-derived exosomes (ADSC-Exos) contain high levels of Show less
Dynamic responsive structural colored materials have drawn increased consideration in a wide range of applications, such as colorimetric sensors and high-safety tags. However, the sophisticated intera Show more
Dynamic responsive structural colored materials have drawn increased consideration in a wide range of applications, such as colorimetric sensors and high-safety tags. However, the sophisticated interactions among the individual responsive parts restrict the advanced design of multimodal responsive photonic materials. Inspired by stimuli-responsive color change in chameleon skin, a simple and effective photo-crosslinking strategy is proposed to construct hydroxypropyl cellulose (HPC) based hydrogels with multiple responsive structured colors. By controlling UV exposure time, the structural color of HPC hydrogels can be effectively controlled in a full-color spectrum. At the same time, HPC hydrogels showcase temperature and mechanical dual-responsive structural colors. In particular, the microstructure of HPC hydrogels undergoes a transition from the chiral nematic phase to the nematic phase under the action of external stretching, leading to a significant reflection of circularly polarized light (CPL) to linearly polarized light (LPL). Given the diverse responsiveness exhibited by HPC hydrogels and their unique structural transition properties under external forces, we have explored their potential applications as dynamic anti-counterfeiting labels and optical skins. This work reveals the great possibility of using structural colored cellulose hydrogels in multi-sensing and optical displays, opening up a new path for the exploration of next-generation flexible photonic devices. Show less
Postmenopausal women are at elevated risk for osteoporosis and dysregulated lipid metabolism. While the relationship between conventional lipid markers and bone mineral density (BMD) remains controver Show more
Postmenopausal women are at elevated risk for osteoporosis and dysregulated lipid metabolism. While the relationship between conventional lipid markers and bone mineral density (BMD) remains controversial, the association between apolipoprotein B-100 (ApoB-100) (an established independent predictor of atherosclerosis) and bone metabolism in postmenopausal women remains poorly understood. This study investigated the relationship between ApoB-100 and lumbar BMD in postmenopausal women, with specific focus on potential inflammatory and platelet-mediated pathways. We conducted a cross-sectional study of 1,429 postmenopausal women who underwent health screening at the First Affiliated Hospital of Xinxiang Medical University between January 2022 and December 2024. ApoB-100 levels were measured by immunoturbidimetry, and lumbar BMD was assessed using low-dose chest CT imaging. Participants were stratified into tertiles based on ApoB-100 levels. We employed univariate and multivariate regression analyses to evaluate the relationship between lumbar BMD and ApoB-100. Generalized additive models with smooth curve fitting were used to characterize the linear relationship. Subgroup analyses assessed the consistency of associations across different populations, while mediation models quantified the intermediary roles of the neutrophil-to-lymphocyte ratio (NLR) and platelet count. After multivariate adjustment, ApoB-100 demonstrated a significant independent negative correlation with lumbar BMD (β=-6.37, 95%CI: -9.26 to -3.49). This association was more pronounced in women younger than 60 years (β=-10.18, 95%CI: -13.94 to -6.42), those with BMI≥28kg/m² (β=-10.73, 95%CI: -15.31 to -0.86), and those without hypertension (β=-7.3, 95%CI: -10.42 to -4.19). Mediation analysis revealed that NLR accounted for 8.17% of the negative association between ApoB-100 and lumbar BMD, while platelet count showed a suppressive indirect association (20.60%). ApoB-100 exhibits an independent negative association with lumbar BMD in postmenopausal women, partially mediated through inflammatory and platelet pathways. These findings support the potential utility of ApoB-100 as a biomarker for osteoporosis risk assessment in postmenopausal women, particularly within specific high-risk subgroups. Show less
The dysregulation of T cell differentiation was associated with cognitive impairment. Recently, the peripheric β-secretase (BACE1) has been suggested as a regulator of T cell differentiation, which wa Show more
The dysregulation of T cell differentiation was associated with cognitive impairment. Recently, the peripheric β-secretase (BACE1) has been suggested as a regulator of T cell differentiation, which was increased in both cognitive impairment (CI) and type 2 diabetes mellitus (T2DM) in CI patients. However, the relationship between T cell dysfunction and CI remains unclear. To address this question, we measured T cell subtypes and BACE1 enzyme activity in a clinical cohort and 5xFAD mice. We found that both IFNγ+ Th1 and Tc1 cells were increased in the CI and T2DM-CI groups, which were associated with worsening cognitive function. The elevated IFNγ + Th1 and Tc1 cells were also observed in 8-month-old 5xFAD mice. The elevated BACE1-mediated INSR cleavage was associated with increased IFNγ + Th1 and Tc1 cells. These findings demonstrate the potential role of elevated BACE1 in IFNγ+ T cells and CI. Show less
The feeding rhythm is a major temporal regulator of metabolic physiology, yet its impact on microbiome-derived functional traits relevant to cardiometabolic disease remains insufficiently understood. Show more
The feeding rhythm is a major temporal regulator of metabolic physiology, yet its impact on microbiome-derived functional traits relevant to cardiometabolic disease remains insufficiently understood. Our previous work demonstrated that ad libitum, daytime-restricted, and nighttime-restricted feeding produce markedly different atherosclerotic outcomes in Apoe Show less
This study aims to identify oxidative stress-related genes (OSGs) in papillary thyroid carcinoma (PTC) and their common targets with resveratrol. Oxidative stress-related differentially expressed gene Show more
This study aims to identify oxidative stress-related genes (OSGs) in papillary thyroid carcinoma (PTC) and their common targets with resveratrol. Oxidative stress-related differentially expressed genes (OS-DEGs) were identified by intersecting datasets. The screened core genes were utilized to construct a prognostic model, and their prognostic value, along with their associations with clinical pathological characteristics and immune infiltration, was assessed. Subsequently, the core targets at the intersection of resveratrol and oxidative stress (OS) in PTC were screened, and their binding properties with resveratrol were analyzed. By conducting cross-database analysis, 38 OS-DEGs were identified, and 3 core genes APOE、CDKN2A、APOD were determined. The prognostic model based on core genes exhibited robust prognostic capabilities. The core genes displayed significant correlations with various clinical pathological parameters and a range of immune cells. Additionally, 13 targets of resveratrol for antioxidative stress were screened from databases. 6 high-performing targets, JUN, TGFB1, BCL2, CDKN1A, FOS, ICAM1, were revealed by topological analysis, all exhibiting binding energies lower than - 5.0 kcal/mol. Our study is the pioneering research to provide new insights into the diagnosis, prognosis, and treatment of PTC through the analysis of OSGs, presenting potential clinical implications. Furthermore, this research reveals the molecular functions associated with resveratrol and its pharmacological targets regulating OS in PTC for the first time. Show less
In Traditional Chinese Medicine (TCM), dampness is a pathogenic factor arising from impaired production and transportation of bodily fluids. While Fuling Zexie decoction (FLZXD) has demonstrated thera Show more
In Traditional Chinese Medicine (TCM), dampness is a pathogenic factor arising from impaired production and transportation of bodily fluids. While Fuling Zexie decoction (FLZXD) has demonstrated therapeutic efficacy in dampness constitution (DC) treatment, the material basis underlying its constitutional modulatory effects remains unclear. This study proposes objective indicators for the differentiation and therapeutic evaluation of DC and elucidates the material basis of FLZXD in DC treatment. Serum exosome proteomic profiling was conducted across two independent cohorts to identify DC-related indicators and assess the therapeutic efficacy of FLZXD in DC-associated hyperlipidemia (DC-hyperlipidemia). The bioactive compounds of FLZXD were prioritized through a comprehensive analysis of patent documentation and network pharmacology, with subsequent validation of DC-related targets using enzyme-linked immunosorbent assay (ELISA). Proteomic analysis of serum exosomes revealed signatures that differentiate individuals with a balanced constitution (BC) from those with DC. The differentially expressed proteins (DEPs) were enriched predominantly in pathways related to the complement cascade and cardiovascular diseases. FLZXD demonstrated therapeutic efficacy against DC-hyperlipidemia, as evidenced by the reversal of DEPs expression following treatment, which was supported by the patentable findings and network pharmacology analysis. Through experimental validation and pharmacological evidence, the active herbs of FLZXD (Fuling, Zexie and Baizhu, collectively referred to as FZB) were identified, and a total of 73 putative therapeutic targets involved in the dampness-resolving effects of FZB were revealed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment further confirmed that FLZXD exerts its anti-dampness effects primarily through regulation of the complement and coagulation cascades. Among eight candidate indicators specifically associated with DC, four proteins were validated via ELISA, indicating potential utility for the differentiation of DC. The sensitivity (%), specificity (%), fold change (FC), p-value, and area under the curve (AUC) for each indicator were as follows: apolipoprotein B-100 (APOB) (100.00, 80.00, 0.63, 0.0051, 0.94), complement factor H-related protein 1 (CFHR1) (90.00, 100.00, 0.55, 0.0001, 0.98), alpha-1-acid glycoprotein 1 (ORM1) (100.00, 80.00, 0.71, 0.0043, 0.92), and pigment epithelium-derived factor (SERPINF1) (90.00, 70.00, 0.66, 0.0002, 0.87). The integrative approach, combining proteomic profiling, network pharmacology analysis, and clinical validation, establishes an integrative approach for research on TCM constitutions. This approach provides (1) molecular insights into the differentiation of DC, (2) a foundation for mechanism-based, targeted therapeutic strategies, and (3) enhanced patient stratification to support personalized treatment approaches. Show less
Diabetic retinopathy (DR) is the main cause of blindness worldwide, and its prevalence rate is constantly rising. More in-depth exploration of its risk factors and pathogenic mechanisms is needed. Thi Show more
Diabetic retinopathy (DR) is the main cause of blindness worldwide, and its prevalence rate is constantly rising. More in-depth exploration of its risk factors and pathogenic mechanisms is needed. This study systematically identified potential therapeutic targets for DR by evaluating causal effects of 16,989 genes and 2,923 proteins on DR/subtypes via two-sample Mendelian randomization (MR), validated with colocalization/Summary-data-based Mendelian randomization (SMR). National Health and Nutrition Examination Survey (NHANES) 1999-2010 cross-sectional data (weighted logistic/Restricted cubic spline (RCS)) pinpointed key risk factors; MR explored their links to DR subtypes. Bioinformatics (bulk and single-cell transcriptomics) analyzed molecular mechanisms of shared targets (gene expression, immune infiltration, pathway enrichment). Machine learning selected key targets for models. Finally, two-step mediation MR examined how targets regulate DR via risk factors. This study identified 64 core targets with causal links to DR. Subtype analysis revealed 2,128 causal genes and subtype-specific targets (e.g. 52 for background DR, 66 for proliferative DR). SMR validated these findings. NHANES data highlighted body mass index (BMI), stroke, hypertension (HBP), and C-reactive protein (CRP) as key DR risk factors, confirmed by MR. Transcriptomics identified 29 differentially expressed genes associated with both risk factors and DR, linked to immune cell regulation. Machine learning selected core targets (LY9, WWP2, etc.) and built a nomogram for DR risk prediction. Functional enrichment showed these targets enriched in chemokine/cytokine and immune-inflammatory pathways. Two-step mediation MR further revealed LY9, ARHGAP1, and WWP2 influence DR subtypes via regulating BMI, CRP, and HBP. This study systematically elucidates the key risk factors, potential molecular mechanisms, and core regulatory targets of DR through multi-omics integration, causal inference, and bioinformatics approaches. The results indicate that inflammation, immune dysregulation, and metabolic disorders play crucial roles in the pathogenesis of DR. Key genes such as LY9, ARHGAP1, and WWP2 could serve as potential intervention targets, offering theoretical foundations and strategic support for early warning and precision treatment of DR. Show less